Cancer Chemotherapy lacks the quantitative tissue-specific dosimetry now available to the radiotherapist. The aim of this grant is to improve the reliability of chemotherapeutic intervention by simulating the detailed impact of specific antitumor drugs. We have developed computer-based mathematical models capable of simulating cell population growth in biologically verifiable cell-kinetic terms. We have also simulated the extracellualer and intracellular distribution of ara-C and its metabolities by tissue. We have begun to study the interaction of cell growth and chemotherapy in a quantitative way consistent with detailed biochemical data. We propose to integrate and extend these cell-kinetic and pharmacokinetic models so that an explicit and quantitative dosimetry can be achieved. We propose to complete our model of bone-marrow proliferation and to extend our kinetic studies to the cellular behavior of lymphomas as well as leukemias. FORTRAN programs have already been provided to other investigators and more will be as additional useful simulations are developed. BIBLIOGRAPHIC REFERENCES: "Cell Kinetic Models of Transient States: A Preliminary Investigation of Lymphocyte Stimulation," J. Aroesty, T. Lincoln, P. Morrison, and G. Carter, Proceedings of the 29th Annual M.D. Anderson Symposium on Fundamental Cancer Research, 1977. "Analysis of High Dose Methotrexate Clinical Trial Data Using CLINFO," T. L. Lincoln, W. H. Isacoff, G. F. Groner, K. L. Willis, and P. F. Morrison, published Environmental Health: Quantitative Methods, Ed. Alice S. Whittemore, SIAM, Philadelphia, 1976, p. 197.